Biocompatibility and Osteochondral Regenerative Potential of Hydroxyapatite-Based Hydrogels in a Vietnamese Pig Knee Defect Model

Background/Objectives: Articular cartilage and osteochondral defects have limited intrinsic healing capacity. This study evaluated the biocompatibility and in vivo regenerative potential of two novel hydroxyapatite-based hydrogels — Simplex Gel (hydroxyapatite/hydroxyethyl cellulose) and Complex Gel (additionally enriched with sodium hyaluronate and chondroitin sulfate) — compared with a commercial hyaluronic-acid control (Reviscon® 1%). Methods: Cytotoxicity (MTT assay, MRC-5 fibroblasts) and genotoxicity (alkaline comet assay, human peripheral blood lymphocytes) were assessed in vitro. In vivo, six Vietnamese pigs received a superficial chondral or a deeper osteochondral defect on the tibial condyle of the right knee, treated with Reviscon®, Simplex Gel, or Complex Gel. After 12 weeks, sections were stained (H&E, Mallory–Azan, Picrosirius Red, PECAM-1) and analyzed stereologically (n = 15 sections/bone). Results: Both gels were non-genotoxic and only weakly to moderately cytotoxic at the two highest concentrations (ISO 10993-5). All treatments achieved complete defect filling with regenerated cartilage and bone, without necrosis, inflammation, or other pathological changes. Complex Gel produced the most pronounced regenerative response, with the highest cell numerical densities and the most intense collagen deposition. Conclusions: Both hydrogels, particularly Complex Gel, are biocompatible and support osteochondral regeneration in a large-animal knee model, warranting further preclinical development.